Based on cytotoxic T lymphocyte (CTL) epitopes from CMV pp65, the principal CTL target for CMV, a novel candidate lipopeptide vaccine has been developed. It is composed of the HLA A*0201-restricted CTL epitope from pp65 covalently attached to a powerful synthetic T-helper epitope, and lipidated at the amino terminus. The test-of-concept for this novel lipopeptide CMV vaccine has been shown using an HLA A2.1 transgenic murine model. The goal of this project is to characterize the immune response to CMV in persons treated with HAART (highly active anti-retroviral therapy) and determine if this immunity can be boosted by lipopeptide immunization. In a three-way collaboration, the City of Hope team will conduct the in vitro measurements of immunity; and the team at the Los Angeles County Medical Center/University of Southern California (LAC/USC) will identify patients, obtain specimens for in vitro measurements, and vaccinate eligible patients. The third team, Peninsula Laboratories, will be responsible for the synthesis and production of lipopeptide vaccine under FDA-approved conditions. Individuals with HIV infection will be studied to understand the cellular immune response to CMV. Information not currently known despite the fact that CMV-associated diseases, including retinitis, enteritis, and encephalitis have been a leading cause of morbidity and mortality in this population, and that CMV could be linked to HIV progression. These studies are important because of the need to explain recent reports indicating less CMV disease with HAART, but the occasional case of CMV retinitis despite recovery to >200 CD4+ T cell counts. At LAC/USC, approximately 70% of new AIDS clinic patients are naive to HAART and will be evaluated for changing CMV immune repertoire during the course of HAART treatment and CD4+ T cell recovery. These studies are aimed at discovering whether immunoprophylaxis against CMV is possible or warranted in individuals undergoing HAART. The strategy of immunization in the setting of HIV-1 infection and HAART in patients with diverse DLA alleles will be built upon a concurrent demonstration of the clinical efficacy of the HLA A2.1-restricted CMV pp65 lipopeptide vaccine in patient volunteers.